Bacteria alter gene expression while adapting to their environments. In some cases, gene expression changes in response to contact with abiotic surfaces. We show that Streptococcus gordonii, a model Gram-positive commensal bacterium, appears to regulate surface protein presentation in response to specifically engaging MUC5B. During biofilm formation on MUC5B, presentation of SGO_0707 on the cell wall and down-regulation of SGO_0890 and SGO_1487 depend on an intramembrane two-component system (TCS) sensor (SGO_1180). We also report (preliminary data) that the well-studied paired adhesins, SspA and SspB (SspAB), is also required to signal for presentation of SGO_0707 and loss of SGO_0890 and SGO_1487. Somewhat promiscuous in specificity, SspAB binds MUC5B. Hence, SspAB may serve as a receptor to induce an outside-in signal. Since SspAB covalently attaches to the cell wall, the signal to the cell membrane is probably transduced by another associated macromolecule. S. gordonii lipoteichoic acid (LTA) binds high molecular weight mucins, interacts with cell wall proteins, and traverses the cell wall to intercalate with the outer leaflet of the cell membrane. Preventing D-alanylation of S. gordonii LTA causes altered presentation of surface proteins. These data suggest that LTA and SspAB are co-receptors for MUC5B, with LTA serving to transduce a signal to a TCS (SGO_1180 and SGO_1181) to change the surface proteins presented on S. gordonii. We hypothesize, therefore, that S. gordonii SspAB cooperates with LTA to serve as a model signal transducing receptor for MUC5B during biofilm formation. To test our hypothesis and satisfy criteria for an outside-in signaling receptor, we will (1) determine whether both SspA and SspB are required; (2) show whether LTA functions as a co-receptor; (3) characterize response regulator SGO_1181 for signaling and regulation; (4) determine whether the change in surface protein presentation involves transcriptional and post-translational mechanisms; and (5) determine whether SspAB and SGO_1180 signal through intersecting or parallel pathways by performing comparative transcriptome analysis. To characterize the output of receptor signaling (Aims 1-4), we will measure transcription of sentinel genes (i.e., SspA, SspB, SGO_0707, SGO_0890, SGO_1487 and SGO_1180), presentation of sentinel surface proteins (i.e., 0707, 0890, 1487), and 1180 phosphorylation dependence. These experiments will define outside-in signaling in S. gordonii in response to specific surface environmental cues, which had been previously been viewed as a feature of higher organisms. This knowledge could suggest how certain bacteria adapt to changing environments when they must adhere or die.